Evidence for disease-regulated transgene expression in the brain with use of lentiviral vectors

2006 ◽  
Vol 84 (1) ◽  
pp. 58-67 ◽  
Author(s):  
Johan Jakobsson ◽  
Nina Rosenqvist ◽  
Karl Mårild ◽  
Denes v. Agoston ◽  
Cecilia Lundberg
Keyword(s):  
Transgene Expression ◽  
Lentiviral Vectors ◽  
The Brain

scholarly journals Stability of Lentiviral Vector-Mediated Transgene Expression in the Brain in the Presence of Systemic Antivector Immune Responses

2005 ◽  
Vol 16 (6) ◽  
pp. 741-751 ◽  
Author(s):  
Evelyn Abordo-Adesida ◽  
Antonia Follenzi ◽  
Carlos Barcia ◽  
Sandra Sciascia ◽  
Maria G. Castro ◽  
...  
Keyword(s):  
Immune Responses ◽  
Transgene Expression ◽  
Lentiviral Vector ◽  
The Brain

DARPP-32 promoter directs transgene expression to renal thick ascending limb of loop of Henle

1995 ◽  
Vol 269 (4) ◽  
pp. F564-F570 ◽  
Author(s):  
S. Blau ◽  
L. Daly ◽  
A. Fienberg ◽  
G. Teitelman ◽  
M. E. Ehrlich
Keyword(s):  
Transgene Expression ◽  
Ectopic Expression ◽  
Medium Size ◽  
Thick Ascending Limb ◽  
Loop Of Henle ◽  
Transcription Start Sites ◽  
Medullary Thick Ascending Limb ◽  
Spiny Neurons ◽  
Adult Kidney ◽  
The Brain

DARPP-32, a dopamine- and adenosine 3',5'-cyclic monophosphate (cAMP)-regulated inhibitor of protein phosphatase-1, is highly colocalized with neuronal and nonneuronal D1-type receptors. DARPP-32 concentration is enriched in the renal outer medulla and in the medium-size spiny neurons of the brain. In the ascending limb of the loop of Henle, DARPP-32 is phosphorylated following stimulation by dopamine and other first messengers, and in this form inhibits the activity of the Na(+)-K(+)-adenosinetriphosphatase pump. For functional analysis of the DARPP-32 promoter in the kidney, we characterized the murine gene. There are two groups of transcription start sites utilized in the brain, but the proximal set appears to be preferentially used in the kidney. In four of four lines of mice carrying a DARPP-32/lacZ transgene with 2.1 kb of 5'-flanking DNA, adult kidney lacZ transgene expression mimicked that of endogenous DARPP-32. There was no ectopic expression in peripheral organs. We conclude that the sequences necessary for direction of DARPP-32 expression to the medullary thick ascending limb are contained within this 2.1-kb fragment.

scholarly journals Identification of cell-type-specific promoters within the brain using lentiviral vectors

Gene Therapy ◽  
2007 ◽  
Vol 14 (7) ◽  
pp. 575-583 ◽  
Author(s):  
J P Chhatwal ◽  
S E Hammack ◽  
A M Jasnow ◽  
D G Rainnie ◽  
K J Ressler
Keyword(s):  
Lentiviral Vectors ◽  
Cell Type ◽  
Cell Type Specific ◽  
The Brain

Modular long-range regulation of Myf5 reveals unexpected heterogeneity between skeletal muscles in the mouse embryo

Development ◽  
2000 ◽  
Vol 127 (20) ◽  
pp. 4455-4467 ◽  
Author(s):  
J. Hadchouel ◽  
S. Tajbakhsh ◽  
M. Primig ◽  
T.H. Chang ◽  
P. Daubas ◽  
...  
Keyword(s):  
Mouse Embryo ◽  
Transgene Expression ◽  
Distal Region ◽  
Trunk Muscles ◽  
Regulatory Sequences ◽  
Spatiotemporal Expression ◽  
Branchial Arches ◽  
Early Expression ◽  
Myogenic Factor ◽  
The Brain

The myogenic factor Myf5 plays a key role in muscle cell determination, in response to signalling cascades that lead to the specification of muscle progenitor cells. We have adopted a YAC transgenic approach to identify regulatory sequences that direct the complex spatiotemporal expression of this gene during myogenesis in the mouse embryo. Important regulatory regions with distinct properties are distributed over 96 kb upstream of the Myf5 gene. The proximal 23 kb region directs early expression in the branchial arches, epaxial dermomyotome and in a central part of the myotome, the epaxial intercalated domain. Robust expression at most sites in the embryo where skeletal muscle forms depends on an enhancer-like sequence located between −58 and −48 kb from the Myf5 gene. This element is active in the epaxial and hypaxial myotome, in limb muscles, in the hypoglossal chord and also at the sites of Myf5 transcription in prosomeres p1 and p4 of the brain. However later expression of Myf5 depends on a more distal region between −96 and −63 kb, which does not behave as an enhancer. This element is necessary for expression in head muscles but strikingly only plays a role in a subset of trunk muscles, notably the hypaxially derived ventral body muscles and also those of the diaphragm and tongue. Transgene expression in limb muscle masses is not affected by removal of the −96/-63 region. Epaxially derived muscles and some hypaxial muscles, such as the intercostals and those of the limb girdles, are also unaffected. This region therefore reveals unexpected heterogeneity between muscle masses, which may be related to different facets of myogenesis at these sites. Such regulatory heterogeneity may underlie the observed restriction of myopathies to particular muscle subgroups.

scholarly journals Toward Tightly Tuned Gene Expression Following Lentiviral Vector Transduction

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1427
Author(s):  
Audrey Page ◽  
Floriane Fusil ◽  
François-Loïc Cosset
Keyword(s):  
Gene Expression ◽  
Transgene Expression ◽  
Lentiviral Vector ◽  
Basic Research ◽  
Lentiviral Vectors ◽  
Retroviral Vectors ◽  
Clinical Applications ◽  
Long Terminal Repeats ◽  
Vector Systems ◽  
Gene Excision

Lentiviral vectors are versatile tools for gene delivery purposes. While in the earlier versions of retroviral vectors, transgene expression was controlled by the long terminal repeats (LTRs), the latter generations of vectors, including those derived from lentiviruses, incorporate internal constitutive or regulated promoters in order to regulate transgene expression. This allows to temporally and/or quantitatively control transgene expression, which is required for many applications such as for clinical applications, when transgene expression is required in specific tissues and at a specific timing. Here we review the main systems that have been developed for transgene regulated expression following lentiviral gene transfer. First, the induction of gene expression can be triggered either by external or by internal cues. Indeed, these regulated vector systems may harbor promoters inducible by exogenous stimuli, such as small molecules (e.g., antibiotics) or temperature variations, offering the possibility to tune rapidly transgene expression in case of adverse events. Second, expression can be indirectly adjusted by playing on inserted sequence copies, for instance by gene excision. Finally, synthetic networks can be developed to sense specific endogenous signals and trigger defined responses after information processing. Regulatable lentiviral vectors (LV)-mediated transgene expression systems have been widely used in basic research to uncover gene functions or to temporally reprogram cells. Clinical applications are also under development to induce therapeutic molecule secretion or to implement safety switches. Such regulatable approaches are currently focusing much attention and will benefit from the development of other technologies in order to launch autonomously controlled systems.

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